Jekyll-Hyde neurotrophins: the story of proNGF.

Neurotrophins promote neuronal survival and differentiation by binding to two classes of cell surface receptors: members of the Trk-family receptor tyrosine kinases and p75(NTR), a member of the tumor necrosis factor receptor superfamily. The discoveries that the unprocessed proneurotrophin peptide is both a preferential high-affinity ligand for p75(NTR) (with minimal affinity for trkA) and a potent inducer of p75(NTR)-mediated neuronal cell death are likely to change our understanding of neurotrophin physiology and our ability to manipulate their signaling pathways.